Autoantibodies to beta 2 GP1 antibodies are detected in the clinical laboratory by different types of assays including immunoassays and functional coagulation assays. Immunoassays for beta 2 GP1 antibodies can be performed using either a composite substrate comprised of beta 2 GP1 plus anionic phospholipid (eg, cardiolipin or phosphatidylserine), or beta 2 GP1 alone. Antibodies detected by immunoassays that utilize composite substrates are commonly referred to as phospholipid or cardiolipin antibodies. Antibodies detected using beta 2 GP1 substrate without phospholipid (so called direct assays) are referred to simply as "beta 2 GP1 antibodies." Some beta 2 GP1 antibodies are capable of inhibiting clot formation in functional coagulation assays that contain low concentrations of phospholipid cofactors. Antibodies detected by functional coagulation assays are commonly referred to as lupus anticoagulants.

The diagnosis of APS requires at least 1 clinical criteria and 1 laboratory criteria be met.(5) The clinical criteria include vascular thrombosis (arterial or venous in any organ or tissue) and pregnancy morbidity (unexplained fetal death, premature birth, severe preeclampsia, or placental insufficiency). Other clinical manifestations, including heart valve disease, livedo reticularis, thrombocytopenia, nephropathy, neurological symptoms, are often associated with APS but are not included in the diagnostic criteria. The laboratory criteria for diagnosis of APS are presence of lupus anticoagulant, presence of IgG and/or IgM anticardiolipin antibody (>40 GPL, >40 MPL or >99th percentile), and/or presence of IgG and/or IgM beta 2 GP1 antibody (>99th percentile). All antibodies must be demonstrated on 2 or more occasions separated by at least 12 weeks. Direct assays for beta 2GP 1 antibodies have been reported to be somewhat more specific (but less sensitive) for disease diagnosis in patients with APS.(4) Anti-cardiolipin and beta 2 GP1 antibodies of the IgA isotype are not part of the laboratory criteria for APS due to lack of specificity.

Strongly positive results for IgG and IgM beta 2 glycoprotein 1 (beta 2 GP1) antibodies (>40 U/mL for IgG and/or IgM) are diagnostic criterion for antiphospholipid syndrome (APS). Lesser levels of beta 2 GP1 antibodies and antibodies of the IgA isotype may occur in patients with clinical signs of APS but the results are not considered diagnostic. Beta 2 GP1 antibodies must be detected on 2 or more occasions at least 12 weeks apart to fulfill the laboratory diagnostic criteria for APS.

The immunoassay for beta 2 glycoprotein 1 (beta 2 GP1) antibodies does not distinguish between autoantibodies and antibodies produced in response to infectious agents or as epiphenomena following thrombosis. For this reason, a single positive test result is not sufficient to meet accepted serologic criteria for the diagnosis of antiphospholipid syndrome (see above).

Comparative studies and interlaboratory proficiency surveys indicate that results of beta 2 GP1 antibody tests can be highly variable and results obtained with different commercial immunoassays may yield substantially different results.(5)